NETosis mediates tick blood pool formation.

Ticks are major public health vectors that rely on long-term extravascular feeding, a process critically dependent on establishing a subcutaneous blood pool. While tick salivary molecules suppress host hemostasis and immunity, the precise mechanism by which vascular integrity is compromised to sustain massive hemorrhage in the deep dermis, outside the tick hypostome's reach, remains a longstanding enigma. Using time-series pathological and multiplex immunohistochemical analyses in a mouse model infected with Haemaphysalis longicornis tick, we redefined the blood pool not as a cystic reservoir, but as a severe inflammatory lesion characterized by massive, diffuse extravasation of red blood cells. We observed that ticks induce pathological angiogenesis, forming fragile microvessels. Crucially, the formation of neutrophil extracellular traps (NETs), known as NETosis surged in clustering neutrophils on Day 3 of feeding, coinciding with the transition to massive hemorrhage. Furthermore, extravasated platelets co-localized with NETs in the hemorrhagic tissue. We propose a sophisticated parasitic strategy, whereby the tick hijacks host immunothrombosis to mediate massive hemorrhage. The dysregulated interaction between NETs and platelets drives a vicious inflammatory cycle, which destroys the fragile, newly formed vasculature and extracellular matrix. This process establishes a blood-soaked, sponge-like stroma, which the tick exploits for efficient blood intake. Our findings redefine the fundamental mechanism of tick feeding success.